1. Field of the Invention
This invention relates to a method for synthesizing a penicillin by reacting a silylate of 6-aminopenicillanic acid and a carboxylic acid halide, and more particularly it relates to such penicillin synthesizing method featuring use of a weakly basic resin as acid coupling agent.
2. Description of the Prior Art
It is known that various kinds of penicillin compositions can be synthesized from 6-aminopenicillanic acid and carboxylic acid halides. The reaction therefor is usually accomplished by first silylating 6-aminopenicillanic acid and then reacting the resultant silylate with a carboxylic acid halide. Since a hydrohalic acid is produced in this reaction, it needs to carry out the reaction in the presence of an acid coupling agent. Heretofore, amines such as dimethylamine, pyridine, quinoline, picoline, etc., have been commonly used as acid coupling agent in said reaction. However, use of such amines involves some serious problems: it is hard to separate such amines from the produced penicillin, and even if an elaborate separating operation is used, there still exists a possibility that a trace amount of amine should be mixed in the product penicillin. Presence of even a trace amount of amine in the product results in various adverse effects such as causing headache, nausea, drowsiness, etc., because of toxicity of amines.
As a result of further researches into the penicillin synthesizing method with no need of using any amine, the present inventors found that the above-said problems can be solved by using an insoluble weakly basic resin having a three-dimensional structure as acid coupling agent, and succeeded in formulating the present invention.